Elucidation of regulatory mechanisms of central nervous system functions by ceramide kinase

• Project/Area Number: 26460060
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Chiba University
• Principal Investigator: Nakamura Hiroyuki 千葉大学, 大学院薬学研究院, 准教授 (20447311)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: セラミドキナーゼ / セラミド-1-リン酸 / 神経突起 / 神経伝達物質 / PC12細胞

Outline of Final Research Achievements

Ceramide kinase produces the bioactive lipid ceramide-1-phosphate. In this study, we determined the role of ceramide kinse on functions of central nervous system. We showed that 1) ceramide kinase regulates the formation of filopodia, 2) NGF induces the formation of ceramide-1-phoshate in PC12 cells, 3) ceramide kinase regulates the release of neurotransmitter.

Research Products

• [Journal Article] Cholesterol-dependent increases in glucosylceramide synthase activity in Niemann-Pick disease type C model cells: Abnormal trafficking of endogenously formed ceramide metabolites by inhibition of the enzyme (2016)
  • Author(s): Hashimoto N, Matsumoto I, Takahashi H, Ashikawa H, Nakamura H, Murayama T
  • Journal Title: Neuropharmacology Volume: 110 Pages: 458-469
  • DOI: 10.1016/j.neuropharm.2016.08.011
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Effects of glycerophospholipids on ceramide kinase activity: Cardiolipin-affected cellular formation of ceramide-1-phosphate (2016)
  • Author(s): Matsuzaki W, Takahashi H, Nakamura H, Murayama T
  • Journal Title: Biological and Pharmacuetical Bulletin Volume: 39 Pages: 1708-1717
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] L-cysteine/d,L-homocysteine-regulated ileum motility via system L and B°,+ transporter: Modification by inhibitors of hydrogen sulfide synthesis and dietary treatments. (2015)
  • Author(s): Yamane S, Nomura R, Yanagihara M, Nakamura H, Fujino H, Matsumoto K, Horie S, Murayama T.
  • Journal Title: Eur J Pharmacol. Volume: 764 Pages: 471-479
  • DOI: 10.1016/j.ejphar.2015.07.042
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Prostaglandin E2-stimulated prostanoid EP4 receptors induce prolonged de novo prostaglandin E2 synthesis through biphasic phosphorylation of extracellular signal-regulated kinases mediated by activation of protein kinase A in HCA-7 human colon cancer cells. (2015)
  • Author(s): Fujino H, Seira N, Kurata N, Araki Y, Nakamura H, Regan JW, Murayama T.
  • Journal Title: Eur J Pharmacol Volume: 768 Pages: 149-159
  • DOI: 10.1016/j.ejphar.2015.10.044
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Eicosanoids Derived From Arachidonic Acid and Their Family Prostaglandins and Cyclooxygenase in Psychiatric Disorders. (2015)
  • Author(s): Yui K, Imataka G, Nakamura H, Ohara N, Naito Y.
  • Journal Title: Curr Neuropharmacol Volume: 13 Pages: 776-785
  • Peer Reviewed
• [Journal Article] Trafficking of acetyl-C16-ceramide-NBD with long-term stability and no cytotoxicity into the Golgi. (2015)
  • Author(s): Makiyama T, Nakamura H, Nagasaka N, Yamashita H, Honda T, Yamaguchi N, Nishida A, Murayama T.
  • Journal Title: Traffic Volume: 16 Issue: 5 Pages: 476-492
  • DOI: 10.1111/tra.12265
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Sphingomyelin Regulates the Activity of Secretory Phospholipase A2 in the Plasma Membrane. (2015)
  • Author(s): Nakamura H, Wakita S, Yasufuku K, Makiyama T, Waraya M, Hashimoto N, Murayama T.
  • Journal Title: J Cell Biochem Volume: in press Issue: 9 Pages: 1898-1907
  • DOI: 10.1002/jcb.25145
  • Peer Reviewed
• [Journal Article] Regulation of alkaline ceramidase activity by the c-Src-mediated pathway. (2014)
  • Author(s): Sasaki H, Toyomura K, Matsuzaki W, Okamoto A, Yamaguchi N, Nakamura H, Murayama T.
  • Journal Title: Arch. Biochem. Biophys. Volume: 550-551 Pages: 12-19
  • DOI: 10.1016/j.abb.2014.03.012
  • Peer Reviewed
• [Journal Article] TRPM8 has a key role in experimental colitis-induced visceral hyperalgesia in mice (2014)
  • Author(s): Hosoya T, Matsumoto K, Tashima K, Nakamura H, Fujino H, Murayama T, Horie S
  • Journal Title: Neurogastroenterol Motil Volume: 印刷中 Issue: 8 Pages: 1112-1121
  • DOI: 10.1111/nmo.12368
  • Peer Reviewed / Open Access
• [Journal Article] Hydrogen sulfide-mediated regulation of contractility in the mouse ileum with electrical stimulation: roles of L-cysteine, cystathionine β-synthase, and K+ channels. (2014)
  • Author(s): Yamane S, Kanno T, Nakamura H, Fujino H, Murayama T.
  • Journal Title: Eur J Pharmacol Volume: 740 Pages: 112-120
  • DOI: 10.1016/j.ejphar.2014.06.054
  • Peer Reviewed
• [Presentation] リン酸化シグナルによるセラミドキナーゼ活性制御機構の解析 (2017)
  • Author(s): 高橋宏昌, 中村浩之, 村山俊彦
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-24
• [Presentation] セラミドキナーゼによる細胞骨格制御機構の解明 (2017)
  • Author(s): 冨澤智史, 中村浩之, 村山俊彦
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-24
• [Presentation] 肺線維症におけるシクロスポリンAの抗線維化作用機構の検討 (2017)
  • Author(s): 山崎璃沙, 粕谷善俊, 藤田哲雄, 梅澤弘毅, 柳原まどか, 中村浩之, 吉野一郎, 巽浩一郎, 村山俊彦
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-24
• [Presentation] セラミドキナーゼは細胞内コレステロールの小胞体への輸送を負に制御する (2017)
  • Author(s): 中村浩之, 江森俊介, 橋本直宏, 松本生, 村山俊彦
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎
  • Year and Date: 2017-03-15
• [Presentation] セラミド-1-リン酸はスフィンゴシンキナーゼ1の活性を直接的に制御する (2017)
  • Author(s): 西野将平, 山下尚大, 中村浩之, 村山俊彦
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎
  • Year and Date: 2017-03-15
• [Presentation] ニーマン・ピック病C型のコレステロール蓄積とスフィンゴ糖脂質との関連性の解明 (2017)
  • Author(s): 橋本直宏, 松本生, 高橋宏昌, 芦川仁美, 中村浩之, 村山俊彦
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎
  • Year and Date: 2017-03-15
• [Presentation] Ceramide kinase is a negative regulator of intracellular cholesterol transport to the endoplasmic reticulum (2016)
  • Author(s): Nakamura H, Emori S, Hashimoto N, Matsumoto I, Murayama T
  • Organizer: 57th International Conference on the Bioscience of Lipids
  • Place of Presentation: Chamonix Mont Blanc, France
  • Year and Date: 2016-09-04
  • Int'l Joint Research
• [Presentation] Role of phosphorylation signaling on activation of group IVA phospholipase A2 by lactosylceramide (2016)
  • Author(s): Yamazaki R, Nakamura H, Moriyama Y, Watanabe K, Tomizawa S, Murayama T
  • Organizer: 57th International Conference on the Bioscience of Lipids
  • Place of Presentation: Chamonix Mont Blanc, France
  • Year and Date: 2016-09-04
  • Int'l Joint Research
• [Presentation] セラミドキナーゼによるアクチン細胞骨格制御機構の解明 (2016)
  • Author(s): 冨澤智史, 中村浩之, 村山俊彦
  • Organizer: 第134回日本薬理学会関東部会
  • Place of Presentation: 那須
  • Year and Date: 2016-07-09
• [Presentation] Trafficking of acetyl-C16-ceramide-NBD with long term stability and no cytotoxicity into the Golgi complex (2016)
  • Author(s): Nakamura H, Makiyama T, Nagasaka H, Yamashita H, Honda T, Yamaguchi N, Nishida A, Murayama T
  • Organizer: The 2016 annual meeting of the American Society for Biochemistry and Molecular Biology (ASBMB)
  • Place of Presentation: San Diego, U.S.A.
  • Year and Date: 2016-04-04
  • Int'l Joint Research
• [Presentation] Cyclosporin A Has Anti-fibrotic Effects in Human Lung Fibroblasts and in Bleomycin-Induced Lung Fibrosis Model Mouse (2016)
  • Author(s): Yamazaki R, Fujita T, Yanagihara M, Nakamura H, Fujino H, Kasuya Y, Murayama T
  • Organizer: The 2016 annual meeting of the American Society for Biochemistry and Molecular Biology (ASBMB)
  • Place of Presentation: San Diego, U.S.A.
  • Year and Date: 2016-04-04
  • Int'l Joint Research
• [Presentation] シクロスポリンAはヒト肺線維芽細胞および肺線維症モデルマウスにおいて線維化抑制作用を示す (2016)
  • Author(s): 山崎璃沙, 藤田哲雄, 柳原まどか, 中村浩之, 藤野裕道, 村山俊彦
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-26
• [Presentation] O-アシル蛍光性セラミド誘導体の合成と細胞膜透過性 (2016)
  • Author(s): 渡部央, 王亜賓, 長坂伸夫, 橋本直宏, 中村浩之, 村山俊彦, 西田篤司
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-26
• [Presentation] 新規赤色蛍光標識セラミドプローブの合成研究 (2016)
  • Author(s): 王亜賓, 楊井理信, 橋本直宏, 中村浩之, 村山俊彦, 西田篤司
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-26
• [Presentation] 長時間安定的にゴルジ体を標識する新規蛍光標識セラミド誘導体 (2016)
  • Author(s): 中村浩之, 牧山智彦, 長坂伸夫, 山下尚大, 本田拓也, 山口直人, 西田篤司, 村山俊彦
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-26
• [Presentation] ヒト結腸癌HCA-7細胞を用いたヒトEP4プロスタノイド受容体による持続的な新規プロスタグランジンE2産生機構の解明 (2016)
  • Author(s): 藤野裕道, 清良尚史, 倉田直希, 荒木祐美, 中村浩之, John W. REGAN, 村山俊彦
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-26
• [Presentation] スフィンゴミエリンはプラズマメンブレンにおいて分泌型ホスホリパーゼA2の活性を調節する (2016)
  • Author(s): 中村浩之, 脇田樹男, 安福加菜, 牧山智彦, 藁谷未沙, 橋本直宏, 村山俊彦
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-09
• [Presentation] TGF-β1による肺線維化；ラクトシルセラミドによるSmad2/3に対する核局在化制御 (2016)
  • Author(s): 渡邊一祥, 高畠護, 中村浩之, 村山俊彦
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-09
• [Presentation] ラクトシルセラミドによるリン酸化シグナルを介した細胞質型ホスホリパーゼA2α制御機構の解明 (2016)
  • Author(s): 山崎璃沙, 中村浩之, 森山友太, 渡邊一祥, 冨澤智史, 村山俊彦
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-09
• [Presentation] セラミド-1-リン酸によるEphA2の動態制御機構の解明 (2016)
  • Author(s): 成岡詩織, 中村浩之, 西野将平, 山下尚大, 村山俊彦
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-09
• [Presentation] カルジオリピンによるセラミドキナーゼ活性制御機構の解明 (2015)
  • Author(s): 高橋宏昌, 松嵜渉, 中村浩之, 村山俊彦
  • Organizer: 第14回 次世代を担う若手ファーマ・バイオフォーラム2015
  • Place of Presentation: 千葉
  • Year and Date: 2015-09-12
• [Presentation] ニーマン・ピック病C型のコレステロール蓄積とスフィンゴ糖脂質との関連性の解明 (2015)
  • Author(s): 橋本直宏, 松本生, 高橋宏昌, 中村浩之, 村山俊彦
  • Organizer: 第14回 次世代を担う若手ファーマ・バイオフォーラム2015
  • Place of Presentation: 千葉
  • Year and Date: 2015-09-12
• [Presentation] スフィンゴミエリンによる分泌型ホスホリパーゼA2活性制御機構の解明 (2015)
  • Author(s): 橋本直宏, 中村浩之, 脇田樹男, 安福加菜, 牧山智彦, 藁谷未沙, 村山俊彦
  • Organizer: 第132回日本薬理学会関東部会
  • Place of Presentation: 埼玉
  • Year and Date: 2015-07-04
• [Presentation] ラクトシルセラミドによる細胞質型ホスホリパーゼ A2α 活性化機構の解明 (2015)
  • Author(s): 中村浩之, 森山友太, 牧山智彦, 山下尚大, 山崎璃沙, 渡邉一祥, 村山俊彦
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] TGF-β1による肺線維化への免疫抑制剤の影響 (2015)
  • Author(s): 山崎璃沙, 松澤康雄, 川島辰男, 柳原まどか, 中村浩之, 藤野裕道, 村山俊彦
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] Cardiolipin binds to and activates ceramide kianse (2015)
  • Author(s): 松嵜渉, 中村浩之, 村山俊彦
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] Lactosylceramide interacts with and activates cytosolic phospholipase A2 (2014)
  • Author(s): Nakamura H, Moriyama Y, Makiyama T, Emori S, Yamashita H, Yamazaki R, Murayama T
  • Organizer: 54th International Conference on the Bioscience of Lipids 2014
  • Place of Presentation: Aberdeen, Scotland
  • Year and Date: 2014-06-23 – 2014-06-27
• [Presentation] Contrary effects of sphingosine-1-phosphate on expression of α-smooth muscle actin in transforming growth factor β1-stimulated lung fibroblasts (2014)
  • Author(s): Yamazaki R, Kawashima T, Matsuzawa Y, Otake S, Yamaura E, Nakamura H, Fujino H, Murayama T.
  • Organizer: 54th International Conference on the Bioscience of Lipids 2014
  • Place of Presentation: Aberdeen, Scotland
  • Year and Date: 2014-06-23 – 2014-06-27
• [Presentation] リン酸化シグナルによるCerK活性制御機構の解明 (2014)
  • Author(s): 山下尚大, 中村浩之, 藁谷未沙, 成岡詩織, 村山俊彦
  • Organizer: 第13回次世代を担う若手ファーマバイオフォーラム2014
  • Place of Presentation: 富山
  • Year and Date: 2014-06-20 – 2014-06-21
• [Remarks]
  • URL: http://www.p.chiba-u.jp/lab/hinka/
• [Remarks]
  • URL: http://www.p.chiba-u.jp/lab/hinka/index.html
• [Remarks]
  • URL: http://www.p.chiba-u.jp/lab/hinka/index.html
• [Patent(Industrial Property Rights)] 抗線維症剤およびリン酸化Smad核内移行阻害剤 (2016)
  • Inventor(s): 中村浩之, 村山俊彦
  • Industrial Property Rights Holder: 千葉大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-07-07
• [Patent(Industrial Property Rights)] ニーマン・ピック病C型を予防または治療するための医薬組成物 (2015)
  • Inventor(s): 中村浩之, 村山俊彦
  • Industrial Property Rights Holder: 国立大学法人 千葉大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-199969
  • Filing Date: 2015-10-08